“Risk-based monitoring and quality management support our shared goals of both protecting human subjects who are participating in clinical investigations and ensuring the data method is quality data that we can rely on,” Jacqueline Corrigan-Curay, the medical policy director in FDA’s Center for Drug Evaluation and Research, said on July 17 during an event on risk-based monitoring.
“We know many people are doing it, and we want to extend that use,” she said.
Risk-based monitoring is an approach of overseeing clinical trial activities focused on the most critical data elements, procedures, and processes of the clinical investigation to ensure data quality, the protection of research volunteers, and the overall integrity of the clinical trial.
The push for greater adoption of risk-based monitoring is part of an overall agency priority to make the costly, lengthy clinical trial system more efficient without compromising protections of the volunteers or the patients who will eventually use the treatments once they hit the market.
Risk-based monitoring would be much less intensive than current practices where every piece of data from a trial is verified, known as 100 percent source data verification. That can account for a quarter of clinical trial costs, according to the Margolis Center for Health Policy at Duke University.
Clinical Trial Efficiency
Risk-based monitoring must go hand-in-hand with a quality risk assessment and a well-designed protocol, said David Burrow, director of FDA’s Office of Scientific Investigations.
“It sounds pretty elementary, but it’s a common misconception across the board,” he said. People often think they can take a risk-based monitoring strategy and put it on top of an already developed protocol, but that is not the case. “When we talk about risk-based quality management, we talk about these three things together.”
The issue of risk-based, quality monitoring matters because “when FDA has data that are reliable, interpretable, and traceable, we take action on applications with a high degree of certainty in the data,” Burrow said. If FDA inspectors have questions in the data they see during clinical inspections, they could issue an information request to ensure the data are good enough for the agency to make an approval decision.
How to Monitor
FDA regulations require sponsors of investigational drugs and devices to have a plan for monitoring their studies, but they do not dictate how to do it. The agency released guidance on risk-based monitoring in 2013 and followed up with a draft guidance document in 2019. Even though 100 percent source data verification is resource intensive and FDA has encouraged a risk-based approach, risk-based monitoring has not been widely adopted yet, said Gregory W. Daniel, who heads up pharmaceutical and medical device policy portfolio for the Duke-Margolis.
Most of the big pharmaceutical companies have been doing risk-based monitoring for a while now, Tim Rolfe, GlaxoSmithKline’s director of risk-based centralized monitoring, said in the meeting. However, the drug industry has concerns about inconsistent requirements around the world for global development programs. Rolfe, FDA, and European Medicines Agency officials all noted that the two regulators have similar but not identical terms they use for taking a risk-based approach.
Contract research organizations, which carry out clinical trials for pharmaceutical companies, can see increased costs when transitioning to risk-based monitoring, said Nicole Stansbury, who leads risk-based monitoring for contractor Syneos Health.
“As an industry, this is costing us more. So we’re still not meeting that challenge of hitting better data quality and better patient safety and lower costs,” Stansbury said. That shift will require the use of more technologies, reduced source verification, and a move toward more remote or centralized monitoring, she said.
Learn more about the risk-based monitoring event on the Duke University website. Read more in the 2013 FDA guidance on risk-based monitoring and in the 2019 FDA guidance on risk-based monitoring Q&A.
Selected information in the "Pharmaceutical Science Update" is compiled from summaries and articles from Bloomberg BNA.